Yamada Hiromu, Yamana Keita, Kawasaki Riku, Yasuhara Kazuma, Ikeda Atsushi
Applied Chemistry Program, Graduate School of Advanced Science and Engineering, Hiroshima University 1-4-1 Kagamiyama Higashi-Hiroshima 739-8527 Japan.
Division of Materials Science, Graduate School of Science and Technology and Center for Digital Green-innovation, Nara Institute of Science and Technology 8916-5 Takayama-cho Ikoma Nara 630-0192 Japan.
RSC Adv. 2022 Aug 10;12(34):22202-22209. doi: 10.1039/d2ra03837d. eCollection 2022 Aug 4.
In this work, we demonstrate that liposome gels in which liposomes are connected by polyethylene glycol terminated by cholesterol groups at both ends can store hydrophilic and hydrophobic drugs in the gel interiors, inner aqueous phases, and lipid membranes. The addition of cyclodextrins (CDxs) as extrinsic stimuli led to the release of drug-entrapping liposomes due to the interactions between CDxs and cholesteryl groups and/or the alkyl chains of lipids. The addition of aqueous solutions of β-CDx, dimethyl-β-CDx, trimethyl-β-CDx, and γ-CDx (final concentration: 7.5 mM) induced the solation of liposome gels and the release of liposomes accompanying the solation. Furthermore, the addition of β-CDx led to the partial release of hydrophilic drugs encapsulated in the liposomes, although the drug release was scarcely observed in other CDxs. In particular, the addition of trimethyl-β-CDx, which has low cytotoxicity, accelerated solation, and cationic liposomes released from the gels were effectively taken up by murine colon cancer (Colon26) cells. Thus, we propose that liposomes released from liposome gels can function as drug carriers.
在本研究中，我们证明了一种脂质体凝胶，其中脂质体通过两端由胆固醇基团封端的聚乙二醇相连，能够将亲水性和疏水性药物储存在凝胶内部、内水相和脂质膜中。作为外部刺激加入环糊精（CDxs）后，由于CDxs与胆固醇基团和/或脂质的烷基链之间的相互作用，导致包裹药物的脂质体释放。加入β-环糊精、二甲基-β-环糊精、三甲基-β-环糊精和γ-环糊精的水溶液（终浓度：7.5 mM）会诱导脂质体凝胶的溶胶化以及伴随溶胶化过程的脂质体释放。此外，加入β-环糊精会导致脂质体中包裹的亲水性药物部分释放，而在其他环糊精中几乎未观察到药物释放。特别是，加入具有低细胞毒性、加速溶胶化作用的三甲基-β-环糊精后，从凝胶中释放的阳离子脂质体能够被小鼠结肠癌（Colon26）细胞有效摄取。因此，我们提出从脂质体凝胶中释放的脂质体可以作为药物载体发挥作用。
